Chronic lymphocytic leukemia treatment algorithm 2018

Abstract

The treatment landscape for patients with chronic lymphocytic leukemia (CLL) has changed considerably with the introduction of very effective oral targeted therapies (such as ibrutinib, idelalisib, and venetoclax), and next-generation anti-CD20 monoclonal antibodies (such as obinutuzumab). These agents lead to improved outcomes in CLL, even among patients with high-risk features, such as del17p13 or TP53 mutation and unmutated immunoglobulin heavy chain (IGHV) genes. Each of these treatments is associated with a unique toxicity profile; in the absence of randomized data, the choice of one type of treatment over another depends on the co-morbidities of the patient. Chemoimmunotherapy still plays an important role in the management of previously untreated CLL patients, particularly among young fit patients who have standard risk FISH profile and mutated IGHV genes. Richter’s transformation of CLL remains a difficult complication to treat, although therapy with programmed death 1 inhibitors such as pembrolizumab and nivolumab has shown impressive responses in a subset of patients. Our ability to risk stratify CLL patients continues to evolve; the CLL-International Prognostic Index (CLL-IPI) is the best validated tool in predicting time to first therapy among previously untreated patients. This review summarizes the current approach to risk stratification and management of CLL patients.

HIF-1α is over-expressed in leukemic cells from TP53-disrupted patients and is a promising therapeutic target in chronic lymphocytic leukemia

“…Chronic lymphocytic leukemia (CLL) patients with high-risk genomic features such as disruption of the TP53 gene (i.e. del(17p) and TP53 mutations) respond poorly to chemoimmunotherapy and frequently relapse [1][2][3][4][5][6][7][8][9] . Significant advances have been made in the treatment of CLL following the introduction of Bruton tyrosine kinase (BTK) inhibitors 10 .…”

Prognosis and new therapeutic approaches in chronic lymphocytic leukemia treatment

“…U pomenutoj studiji, neutropenija, transaminitis i dijareja i/ili kolitis češće su se javljali kod bolesnika u grani sa idelalisibom (39). Na osnovu ovih rezultata, idelalisib je, u kombinaciji sa rituksimabom (monoklonsko anti-CD20 antitelo prve generacije), dobio odobrenje FDA i EMA 2014. godine za lečenje R/R HLL bolesnika kod kojih bi primena monoterapije rituksimabom bila adekvatna terapija s obzirom na komorbiditete (31,40). Američka agencija za hranu i lekove je odobrila i primenu monoterapije idelalisibom kod bolesnika sa relapsom limfoma malih limfocita (engl.…”

“…Američka agencija za hranu i lekove je odobrila i primenu monoterapije idelalisibom kod bolesnika sa relapsom limfoma malih limfocita (engl. small lymphocytic lymphoma, SLL) kod kojih su primenjene najmanje dve linije sistemske terapije (31,40). Uočen je veći rizik za određene infekcije, te se savetuje profilaksa Pneumocystis jirovecii pneumonije i monitoring reaktivacije citomegalovirusa (CMV) (41).…”

Tumor Suppressors in Chronic Lymphocytic Leukemia: From Lost Partners to Active Targets

“…The presence on peripheral blood of ≥5000 lymphocytes/µL with the typical immunophenotypic co-expression of T cell marker CD5 and B cell surface antigens CD19, CD20, and CD23 with low levels of monoclonal immunoglobulin defines CLL diagnosis according to the international working group of CLL [3,4]. The clinical course of CLL is variable, as extensively reviewed [5]. Chemoimmunotherapy was recognized as the standard of treatment for young patients with CLL (below 65 years of age) who can benefit from fludarabine and cyclophosphamide with anti-CD20 monoclonal antibody.…”